CXCR4-targeted PET/CT Imaging in Hematological Malignancies

Official title

An Exploratory, Open-Label, Single Center Study of CXCR4-targeted PET/CT Imaging for Evaluation of Hematological Malignancies

Overview

Hematological malignancies continue to pose significant clinical challenges due to their high incidence, heterogeneous biology, and substantial mortality. Although 18F-FDG PET/CT remains the most commonly used molecular imaging modality, its limited specificity can result in false-positive or false-negative findings, especially in indolent or low-metabolism subtypes, thereby hampering accurate diagnosis, staging, and therapeutic evaluation. C-X-C chemokine receptor type 4 (CXCR4) is frequently overexpressed in a broad spectrum of hematologic malignancies and correlates with aggressive disease and unfavorable outcomes. CXCR4-targeted molecular imaging using \^68Ga-pentixafor PET/CT has shown promise for improved disease characterization. This prospective study aims to systematically compare 68Ga-pentixafor PET/CT with 18F-FDG PET/CT in terms of diagnostic performance, staging accuracy, risk stratification, and prognostic relevance in patients with hematological malignancies. Furthermore, the study will incorporate artificial intelligence-based image analysis to enhance lesion detection, automate quantitative assessments, and support personalized clinical decision-making.

Detailed description

Hematological malignancies encompass a heterogeneous group of neoplasms originating from the bone marrow and lymphatic system. Despite advances in therapeutic strategies, the prognosis for many subtypes remains suboptimal, and accurate initial evaluation is critical for appropriate treatment planning. \^18F-FDG PET/CT is routinely used for functional imaging in these patients; however, its diagnostic utility is limited by variable glucose metabolism across disease subtypes and inflammatory uptake, which can lead to misclassification.

CXCR4, a chemokine receptor involved in tumor proliferation, invasion, and microenvironmental interactions, is overexpressed in numerous hematologic malignancies and has emerged as a molecular target for both imaging and therapy. 68Ga-pentixafor, a CXCR4-targeted PET radiotracer, has demonstrated superior lesion detection in preliminary studies, particularly in diseases with low 18F-FDG avidity.

This prospective study will investigate the clinical utility of 68Ga-pentixafor PET/CT in patients with newly diagnosed or relapsed hematological malignancies. Comparative analyses with 18F-FDG PET/CT will be performed to assess concordance, staging accuracy, and association with known risk stratification systems. Longitudinal follow-up will be conducted to evaluate the prognostic relevance of imaging findings.

In parallel, the study will explore the application of artificial intelligence (AI) techniques, including deep learning-based image segmentation and radiomic feature extraction, to enhance diagnostic precision and support risk-adapted management strategies. AI-driven models will be developed and validated to predict disease burden, progression, and survival, thereby contributing to personalized medicine in hematologic oncology.

Interventions

• Drug 68Ga-pentixafor
  All participants undergo intravenous administration of 68Ga-pentixafor (1.85-3.71 MBq/kg body weight).
• Device PET/CT
  PET/CT imaging is performed 1 h after intravenous injection of 68Ga-pentixafor.

Primary outcome measures

• Diagnostic Accuracy of 68Ga-pentixafor PET/CT Compared to 18F-FDG PET/CT in Hematological Malignancies [Time frame: Two years]
• Concordance of [⁶⁸Ga]Ga-pentixafor PET/CT with Standard Clinical Staging Systems [Time frame: Two years]
• Predictive Value of [⁶⁸Ga]Ga-pentixafor PET/CT Parameters for Progression-Free Survival [Time frame: Four years]
• Predictive Value of [⁶⁸Ga]Ga-pentixafor PET/CT Parameters for Overall Survival [Time frame: Four years]
• Dice Similarity Coefficient (DSC) for AI-based lesion segmentation [Time frame: Two years]

Secondary outcome measures (3)

• Correlation Between CXCR4 Expression and [⁶⁸Ga]Ga-pentixafor PET/CT Parameters [Time frame: Two years]
• Correlation between del(17p) status and TLU on [68Ga]Ga-pentixafor PET/CT [Time frame: Two years]
• Radiogenomic Model for Risk Prediction Using AI [Time frame: Two years]

Eligibility criteria

Inclusion criteria

• Volunteer to participate and sign an informed consent form;
• 18 ≤ Age ≤ 90 years;
• Patients with highly suspected, or newly diagnosed, or relapsed hematological malignancies;
• Willing and able to follow schedule visits, treatment plans and laboratory tests.

Exclusion criteria

• pregnancy or breastfeeding;
• Allergic to CXCR4-targeted tracers or excipients;
• Fasting blood glucose level exceeded 11.0 mmol/L prior to injection of 18F-FDG;
• Those who cannot complete PET/CT scan, including inability to keep supine, claustrophobia, radiation phobia, etc.;
• Researchers think it is inappropriate to participate in this clinical trial for patients with poor compliance or other unsuitable factors.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

China · 1 center

• Zhongnan Hospital of Wuhan University — Wuhan

Publications

• Herrmann K, Lapa C, Wester HJ, Schottelius M, Schiepers C, Eberlein U, Bluemel C, Keller U, Knop S, Kropf S, Schirbel A, Buck AK, Lassmann M. Biodistribution and radiation dosimetry for the chemokine receptor CXCR4-targeting probe 68Ga-pentixafor. J Nucl Med. 2015 Mar;56(3):410-6. doi: 10.2967/jnumed.114.151647. Epub 2015 Feb 19. PMID 25698782
• Pan Q, Cao X, Luo Y, Li J, Feng J, Li F. Chemokine receptor-4 targeted PET/CT with 68Ga-Pentixafor in assessment of newly diagnosed multiple myeloma: comparison to 18F-FDG PET/CT. Eur J Nucl Med Mol Imaging. 2020 Mar;47(3):537-546. doi: 10.1007/s00259-019-04605-z. Epub 2019 Nov 27. PMID 31776631
• Duell J, Krummenast F, Schirbel A, Klassen P, Samnick S, Rauert-Wunderlich H, Rasche L, Buck AK, Wester HJ, Rosenwald A, Einsele H, Topp MS, Lapa C, Kircher M. Improved Primary Staging of Marginal-Zone Lymphoma by Addition of CXCR4-Directed PET/CT. J Nucl Med. 2021 Oct;62(10):1415-1421. doi: 10.2967/jnumed.120.257279. Epub 2021 Feb 12. PMID 33579803
• Chen J, Tang S, Liu L, Tian Y, Wang Y, Xiao Z, Xing D, Zhou F, Li C, He Y. [68Ga]Ga-Pentixafor PET/CT for Durie-Salmon PLUS staging and risk stratification in newly diagnosed multiple myeloma. Eur J Nucl Med Mol Imaging. 2026 Jun;53(7):4572-4586. doi: 10.1007/s00259-026-07813-6. Epub 2026 Feb 28. PMID 41760826

Identifiers

NCT: NCT05255926 · ZNYYHYXK0002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗